Viral Dynamics of SARS-CoV-2 in Critically Ill Allogeneic Hematopoietic Stem Cell Transplant Recipients and Immunocompetent Patients with COVID-19

Roedl, Kevin; Heidenreich, Silke; Pfefferle, Susanne; Jarczak, Dominik; Urbanowicz, Tatiana; Nörz, Dominik; Aepfelbacher, Martin; Kluge, Stefan; Lütgehetmann, Marc; Christopeit, Maximilian; Wichmann, Dominic

doi:10.1164/rccm.202009-3386le

Cited by 13 publications

(13 citation statements)

References 10 publications

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“…Severe COVID-19 and the need for mechanical ventilation were higher in allo-HCT recipients compared with auto-HCT recipients, similar to the findings of Verma et al [13] . The mortality rate in 11 patients admitted to the ICU was 73%, consistent with a previous report of 83% mortality in 6 HCT recipients admitted to the ICU [30] .…”

Section: Discussionsupporting

confidence: 90%

“…We report a significantly higher mortality of 16% with COVID-19 in HCT/CAR-T therapy recipients compared with the observed case fatality ratio of 1.8% in the general US population [26] . Previous studies have reported a COVID-19-related mortality rate of approximately 20% in HCT/CAR-T therapy recipients [ 13 , 20 , 21 , 22 , 27 , 28 , 29 , 30 ]. In a US cohort of 34 HCT recipients, Verma et al [13] reported 21% mortality from COVID-19, with most of the deaths in the allo-HCT group (25%), which is comparable to the 28% mortality rate of allo-HCT recipients in our cohort.…”

Section: Discussionmentioning

confidence: 99%

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Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

Mushtaq

Shahzad

Chaudhary

et al. 2021

Transplantation and Cellular Therapy

103

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Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020, and has caused more than 600,000 deaths in the United States at the time of this report. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have a higher risk of mortality with COVID-19 owing to profound immune dysregulation. In this study, we investigated the impact of SARS-CoV-2 in HCT/CAR-T therapy recipients. This single-center prospective study included all (n = 58) adult HCT/CAR-T recipients who were diagnosed with COVID-19 at the University of Kansas Medical Center between March 2020 and May 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (IBM, Armonk, NY). Bivariate analyses, using the chi-square and t-test, and logistic regression analyses were conducted. The study included 58 HCT/CAR-T patients who acquired SARS-CoV-2 infection, including recipients of allogeneic HCT (n = 32), autologous HCT (n = 23), and CAR-T therapy (n = 3). The median patient age was 58 years (range, 24 to 77 years), and 64% were males. The median time from HCT/CAR-T therapy to SARS-CoV-2 infection was 17.7 months (range, 0.2 to 201.9 months), and 22% of the patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T therapy. The primary hematologic disorders were plasma cell (36%), myeloid (38%), and lymphoid (26%) malignancies. Myeloablative conditioning was performed in 62% of patients. Donors were autologous (45%), matched sibling (15%), matched unrelated (21%), and haploidentical (19%). Prior history of grade II-IV acute graft-versus-host disease (GVHD), active GVHD, and current immunosuppressive therapy (IST) was noted in 22%, 31%, and 36% of patients, respectively. Concurrent infections were observed in 19%. Lymphopenia ( P = .049) and high serum ferritin concentration ( P = .020) were associated with mortality. COVID-19 severity was mild in 50% of the patients, moderate in 22%, and severe in 28%. Clinical findings included pneumonia or abnormal chest imaging (in 50%), hypoxia (28%), intensive care unit admission (19%), and mechanical ventilation (10%). Therapies included remdesivir (in 41%), convalescent plasma (35%), dexamethasone (22%), monoclonal antibodies (19%), and tocilizumab (3%). The median duration of viral shedding (positive SARS-CoV-2 PCR) was 7.7 weeks (range, 2 to 18.7 weeks), and 2 patients had a persistent infection for >5 months post-CAR-T therapy. After a median follow-up of 6.1 months (range, 0.5-13.6 months), the mortality rate was 16% in all patients and 28% in allogeneic HCT recipients. Among 9 patients who died, the median survival after SARS-CoV-2 infection was 23 days (range, 14 to 140 days). In survivors with moderate-severe COVID-19, the median time to recovery was 4.2 weeks (range, 1.1 to 24.7 weeks). Among allogeneic HCT...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

Mushtaq

Shahzad

Chaudhary

et al. 2021

Transplantation and Cellular Therapy

103

View full text Add to dashboard Cite

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“…The risk for severe and fatal courses of COVID-19 is particularly high after allogeneic hematopoietic stem cell transplantation (alloSCT) [1][2][3][4]. Cardiovascular and renal morbidity is increased post COVID-19 [5].…”

Section: To the Editormentioning

confidence: 99%

Allogeneic stem cell transplantation in acute leukemia patients after COVID-19 infection

Christopeit

Reichard

Niederwieser

et al. 2021

Bone Marrow Transplant

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“…14 We believe that HSCT patients would certainly benefit if we could find a viral-specific quantitative prognostic parameter that can predict the COVID-19 disease course at the earliest in these immunocompromised patients. In a similar attempt, Roedl et al 15 published a case series of six patients with HSCT or chimeric antigen receptor T-cell therapy who required intensive care unit (ICU) level of care for COVID-19 pneumonia. 15 Unlike the reports by Pujadas et al 11 and Magleby et al, 14 they did not find any correlation to suggest that a high respiratory viral load at admission could correlate with high mortality.…”

Section: Available Literaturementioning

confidence: 99%

“…In a similar attempt, Roedl et al 15 published a case series of six patients with HSCT or chimeric antigen receptor T-cell therapy who required intensive care unit (ICU) level of care for COVID-19 pneumonia. 15 Unlike the reports by Pujadas et al 11 and Magleby et al, 14 they did not find any correlation to suggest that a high respiratory viral load at admission could correlate with high mortality. However, they did find a significant viremia in most of their critically ill patients.…”

Section: Available Literaturementioning

confidence: 99%

A review on recipients of hematopoietic stem cell transplantation patients with COVID-19 infection

Sahu

Siddiqui

2021

Therapeutic Advances in Infection

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For the last few months, various geographical regions and health sectors have been facing challenges posed by the current COVID-19 pandemic. COVID-19 has led to significant disruption in the normal functioning of potentially life-saving therapies of hematopoietic cell transplant and chimeric antigen receptor therapy. As transplant physicians are gaining more information and experience regarding the undertaking of these complex procedures during the ongoing COVID-19 pandemic, we believe it is important to discuss the challenges faced, prognostic risk factors, and outcomes of COVID-19 in post-hematopoietic stem cell transplantation patients based on the available real-world data.

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Viral Dynamics of SARS-CoV-2 in Critically Ill Allogeneic Hematopoietic Stem Cell Transplant Recipients and Immunocompetent Patients with COVID-19

Cited by 13 publications

References 10 publications

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

Allogeneic stem cell transplantation in acute leukemia patients after COVID-19 infection

A review on recipients of hematopoietic stem cell transplantation patients with COVID-19 infection

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